Molecular-based guided therapy shows promise in HCC/H-CCK refractory to atezolizumab/bevacizumab

A recent study has demonstrated the feasibility of molecular-based targeted therapy in patients with hepatocellular carcinoma (HCC)/hepato-cholangiocarcinoma (H-CCK) that progressed while under treatment with atezolizumab/bevacizumab.

In this study, 135 patients with HCC or H-CCK who progressed under atezolizumab/bevacizumab with available tumour frozen samples in one centre benefitted from whole-genome/exome and RNA sequencing. The authors then matched the targeted therapies to genomic alterations following the recommendations of a molecular tumour board and assessed radiological response and overall survival.

Of the patients (median age 57 years, 70 percent male), 20 benefitted from genomic analysis following progression (16 HCC; four H-CCK), and 19 patients had analysable data. Sixty-five percent had metastatic disease, while 45 percent had vascular invasion. Fourteen (76 percent) of the 19 patients had at least one actionable genomic alteration, of whom nine (45 percent) received an adapted targeted therapy.

Palbociclib was given to one patient with H-CCK showing CDK4 amplification, who then achieved a partial radiological response for 16 months. Another patient with H-CCK, high HER2 overexpression, and a high homologous recombination score received trastuzumab/olaparib and had a stable disease.

Furthermore, one patient with an HCC and bi-allelic inactivation of TSC2 achieved a complete radiological response under everolimus. The remaining six HCC patients who received treatment (three with trametinib, two with everolimus, and one with olaparib) had progressive disease.

“[W]hole-genome/-exome and RNA sequencing is feasible on tumour biopsies from patients refractory to atezolizumab/bevacizumab, with a small subset of patients exhibiting at least one actionable genomic alteration and receiving an adapted targeted therapy,” the authors said.

“This proof-of-concept study suggests that this clinical strategy could benefit a small subset of patients. Finally, validation of this approach will be required in a larger cohort of patients,” they added.